Title:Centers of Excellence for Research on Complementary and Alternative Medicine (CERC) [P01]

Announcement TypeThis is a reissue of PAS-03-038, previously released December 4, 2002.

Looking Ahead: As part of the Department of Health and Human Services' implementation of e-Government, during FY 2006 the NIH will gradually transition each grant mechanism to electronic submission through Grants.gov and the use of the SF 424 Research and Related (R&R) forms. Therefore, once the transition is made for a specific grant mechanism, investigators and institutions will be required to submit applications electronically using Grants.gov. For more information and an initial timeline, see http://era.nih.gov/ElectronicReceipt/. NIH will announce each grant mechanism change in the NIH Guide to Grants and Contracts (http://grants.nih.gov/grants/guide/index.html). Specific funding opportunity announcements will also clearly indicate if Grants.gov submission and the use of the SF424 (R&R) is required. Investigators should consult the NIH Forms and Applications Web site (http://grants.nih.gov/grants/forms.htm) for the most current information when preparing a grant application.

This PAR solicits applications for Centers comprised of three or four synergistic, R01-level projects focused on the mechanisms of action of Complementary/Alternative therapies or modalities.

This PAR will use the P01 (Program Project) mechanism.

Up to three awards per year, for up to five years of support, and up to $1.2 million total cost per Center per year will be awarded.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the quality, duration, and costs of the applications received.

Applications may be submitted by domestic, for-profit or non-profit organizations, public or private institutions, such as universities, colleges, hospitals, and laboratories, units of State or local governments, eligible agencies of the Federal government, faith-based or community-based organizations, or units of State or Local Tribal governments.

Eligible principal investigators include all individuals with the skills, knowledge, and resources necessary to carry out the proposed research. Individuals from underrepresented racial and ethnic groups, as well as women and persons with disabilities, are encouraged to apply as PIs. The PI must be able to commit at least 25% effort to the CERC.

The National Center for Complementary and Alternative Medicine (NCCAM) seeks applications for Centers of Excellence for Research on Complementary and Alternative Medicine (CERC), using the NIH Program Project (P01) mechanism. The CERC constitute one component of NCCAM’s multi-faceted Complementary and Alternative Medicine (CAM) research program.

The purpose of the CERC is to provide a vehicle for accomplished researchers to apply their expertise to CAM research questions, with an emphasis on applying cutting-edge scientific approaches to elucidating the mechanisms of action of CAM therapies and modalities. Applications must comprise three to four research projects structured around a central scientific theme that is clearly relevant to CAM.

Some examples of disciplinary approaches of potential interest include:

Molecular biology

Cellular biology

Immunology

Pharmacology

Neurobiology

This list should not be considered to be comprehensive, restrictive, or in priority order.

CERC should be focused around a central scientific theme such as wellness or expectancy, a disease or class of diseases treated using CAM modalities, or a specific CAM modality. Studies using animal models are encouraged. CERC may also include mechanistic studies of human participants, and one Phase I or one Phase II clinical study of modest size, provided such studies are adequately powered to detect a meaningful difference between groups or to validate surrogate markers of disease or clinical endpoints. Applicants planning to propose research involving human subjects should consult the guidelines for NCCAM-supported clinical trials (http://nccam.nih.gov/research/policies/index.htm).

BACKGROUND

NCCAM defines CAM as a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine. NCCAM groups the wide range of CAM modalities into four domains: 1) Mind-Body Medicine; 2) Biologically-based practices; 3) Manipulative and body-based practices; and 4) Energy Medicine. In addition, NCCAM supports studies of whole medical systems, such as Ayurvedic medicine, traditional Chinese medicine, traditional indigenous medical systems, and homeopathy.

Mind-body interventions use a variety of techniques designed to enhance the mind's capacity to affect body functions and symptoms. Mind-body techniques that are considered CAM include yoga; lifestyle behaviors such as tai chi exercise; meditative strategies such as mindfulness meditation; and psychological strategies to manage stress. Also included are therapies that use creative outlets such as visual arts, music or dance. Other techniques that were considered CAM in the past have become mainstream, such as patient support groups and cognitive-behavioral therapy.

Biologically-based practices for prevention and therapy use foods and their components, diets, and dietary supplements (including botanicals, animal-derived products, probiotics and small molecules) and functional foods. Applicants planning to propose studies of biologically-based practices should consult NCCAM’s policy on biologically-active agents used in CAM (http://nccam.nih.gov/research/policies/bioactive.htm).

Manipulative and body-based methods in CAM are based on manipulation and/or movement of one or more parts of the body. Examples include chiropractic or osteopathic manipulation, and massage therapy.

Energy therapies are of two types: 1) Biofield therapies (e.g., Qi gong, Reiki, and therapeutic touch), which are intended to affect energy fields that surround and penetrate the human body, and 2) electromagnetic-based therapies that involve the unconventional use of electromagnetic fields such as pulsed fields, magnetic fields, or alternating or direct current fields.

For many CAM practices the mechanisms of action are poorly understood. Improved understanding of mechanisms through preclinical studies including those using animal models, as well as through mechanistic studies of human participants, should support better-designed studies of efficacy and eventually translate into integrative medical practice.

RESEARCH PRIORITIES

Applicants should consult the NCCAM website (http://nccam.nih.gov/training/centers/index.htm) for relevant information regarding current specific NCCAM research priorities. NCCAM regularly examines and redefines its research priorities in order to fill gaps in its portfolio and capitalize on emerging opportunities to advance CAM research and to leverage the expertise and resources of other NIH Institutes and Centers (ICs) and agencies. Applications substantially similar to those CERC already funded (listed at http://nccam.nih.gov/training/centers/index.htm) may be given lower program priority.

Currently, NCCAM has a substantial financial and intellectual commitment to the study of botanicals primarily through the Dietary Supplement Research Centers Program. Applications previously submitted to RFA-OD-04-002: the Dietary Supplement Research Centers: Botanicals, may be submitted to this PAR only if they are revised to reflect NCCAM’s current research priorities and the focus of the CERC initiative on mechanisms of action. Applications with the same specific aims as applications previously submitted in response to RFA-OD-04-002 will be deemed unresponsive and returned to the applicant.

Applicants who have questions regarding research areas of interest to NCCAM or eligibility for the CERC program should discuss potential proposals with the appropriate NCCAM Program Officer (http://nccam.nih.gov/research/contact/index.htm).

STRUCTURE OF THE CERC

Funded awards must include at least three, and not more than four synergistic, R01-level projects at any given time. CERC should be focused around a central scientific theme such as wellness or expectancy, a disease or class of diseases treated using CAM modalities, or a specific CAM modality. Projects/cores must be synergistic, as defined in Section IV.2 and V.2.e, below.

Center P.I.s must commit at least 25% effort.

Each CERC is required to have an administrative core, which must serve all projects within the CERC. The administrative core is responsible for day-to-day administration, as well as program coordination and ongoing evaluation of the Center. Scientific cores may be included as needed, bearing in mind that each core should be utilized by as many projects as possible. Each scientific core must support at least two projects. Applications must clearly demonstrate how each core will serve the needs of the research program, and how each project will use core resources.

A CERC External Advisory Committee (EAC) will provide guidance to the P.I. Potential EAC members should NOT be named in the application except where the application is a competitive renewal and EAC members from the initial award are proposed to continue to serve on the EAC.

CERC P.I.s and project leaders should plan to participate in an annual, two-day meeting with other NCCAM-funded center P.I.s in the Baltimore-Washington area. Travel costs for this purpose should be included in the proposed budget for the application.

This funding opportunity will use theNIH program project (P01)award mechanism.

As an applicant, you will be solely responsible for planning, directing, and executing the proposed CERC. These awards will support broadly based multidisciplinary research programs that have a well-defined central research focus or objective. An important feature is that the interrelationships among the individual scientifically meritorious projects will result in a greater contribution to the overall program goals than if each project were pursued individually.

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

This Program Announcement will use the NIH program project (P01) award mechanism. A P01 Center grant application (CERC) may request up to five years of support.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The length of award will be determined through the peer review and Council advisory process.

2. Funds Available

In FY 2006, NCCAM will commit up to $3.6 million to fund as many as three new CERC applications in response to this initiative. Applications exceeding $1.2 million total cost in any year will be considered unresponsive and returned without further consideration. The requested direct cost budget for the CERC will include direct and facilities and administrative costs for all subcontracts. However, facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004. Awards pursuant to this PAS are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. At this time, it is not known if this PAR will be reissued; NCCAM may undertake an evaluation of the CERC program before making a decision regarding its continuation. Awards pursuant to this PAS may be made as early as September of the year in which the application is submitted, and may provide up to five years of support.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of NCCAM provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

For-profit organizations

Non-profit organizations

Public or private institutions, such as universities, colleges, hospitals, and laboratories

Units of State government

Units of local government

Eligible agencies of the Federal government

Domestic Institutions

Faith-based or community-based organizations

Units of State Tribal government

Units of Local Tribal government

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.The PI must dedicate at least 25% effort to the CERC.

2. Cost Sharing or Matching

This program does not require cost sharing, matching or cost participation as defined in the current NIH Grants Policy statement.

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

Because the application form has no specific instructions for multi-project applications such as the CERC, consisting of research projects and core(s) interrelated by a common theme, the following instructions are provided for sections of the application form that are to be completed differently than usual. The following instructions describe modifications to the standard instructions on selected items to address the collaborative or interactive nature of the CERC. For all other items in the individual project application, follow the standard instructions.

The instructions below are divided as follows:

CERC application overview, which addresses the overall objectives and unifying theme(s) of this multi-project grant, the relationships among research projects and the cores (including the administrative and organizational structure) and how they will each contribute to the overall objectives and the overall budget.

Specific instructions for individual projects, describing modifications to the standard instructions to address the collaborative/interactive nature of the project.

Specific instructions for the cores, each of which must provide services or resources to at least two research projects.

CERC application overview

This multi-project grant application should be assembled and paginated as a single, complete document.

Face page

Items 1 - 15: complete these items as instructed. This should be the first page of the entire application and all succeeding pages should be numbered consecutively.

Form page 2

Using Form page 2, provide a succinct but accurate description (abstract) of the overall CERC application addressing the major, common theme of the program, as well as the objectives of the individual projects and cores. Do not exceed the space provided.

Under "key personnel", list the P.I., followed by all other key personnel (project leaders, core leaders, consultants) in alphabetical order.

Form page 3 - Table of contents

Do not use Form page 3; a more comprehensive table of contents is needed for a multi-project application.

Bearing in mind that the application will be scientifically reviewed project by project, including the cores, prepare a detailed table of contents that will enable reviewers to locate specific information pertinent to the overall application as well as to each component research project and core. A page reference should be included for the budget for each project and each core, and for letters from the project and core leaders, and from institutional officials, confirming their roles in the proposed Center. Page references for the biographical sketches (clustered at the end of the application) should be provided.

Each research project should be identified by number (e.g. project 1), title, and responsible Project Leader, and each core should be identified by a letter (core A, core B, etc.), title, and responsible Core Leader.

Form page 4 - Detailed budget for initial budget period

Use Form page 4 as a composite budget for the entire CERC application. Indicate the page location of the composite budget in the "Table of Contents." Note: An additional Form page 4 must be used for each individual project and core within the CERC application.

Narrative justification for individual budget categories should be presented for each of the projects and cores.

Form page 5 - Budget for entire proposed CERC period

Complete the total direct cost line entries for all requested budget periods (years) and the total direct cost for entire period of support for each project and core.

Biographical sketch form page

Biographical sketches of all professional personnel for all components should be placed at the end of the entire application (immediately before the Checklist) with the P.I.'s first, followed by those of other key personnel in alphabetical order.

Resources form page

Do not complete for the overall application. Essential information is to be presented in the individual research project and core sections of the application.

Checklist

Complete for the entire application and place at the end of the application package.

Program overview (research plan)

Foreword:

Include a one-page foreword that describes relevant previous collaborative arrangements, if any.

For competitive continuation applications, provide the beginning and ending dates for the period covered since the project was last reviewed competitively. Summarize the previous application’s specific aims and the importance of the findings. Discuss any changes in the specific aims as a result of budget reductions. Discuss the rationale for any changes in the structure of the current proposed Center (as compared to the previously funded CERC).

Include the complete references to appropriate publications and manuscripts accepted for publication that pertain to the CERC as a whole (the reference list is not counted towards the Research Plan page limit). Manuscripts specific to individual projects or cores should be included in the sections specific to the relevant component.

Items a-d (see instructions) are limited to 25 pages. This narrative section summarizes the overall research plan for the multi-project application. The CERC application should be viewed as a confederation of synergistic research projects, each of which is capable of standing on its own scientific merit.

This important section provides the group of investigators an opportunity to give conceptual wholeness to the overall program by giving a statement of the general problem area and by laying out a broad strategy for attacking the problems. Include a section that specifically addresses scientific and/or programmatic synergy between projects, and between projects and proposed cores (e.g., the degree of interaction between projects and with the cores must result in a program where "the whole is greater than the sum of its parts"). Delineate how different components of the CERC, including key personnel, will interact, why they are essential to accomplishing the overall goal of the research, and how the combined resources create capabilities that are more than the sum of the parts. Provide examples of ways in which the proposed projects/cores may scientifically inform and enhance each other. Indicate the contribution of each project and core to the overall scheme, keeping in mind that each core must be utilized by at least two proposed projects. Include a chart showing the percentage of core activities required for support of each project throughout the requested funding period. Summarize special features of the environment and/or resources that make this application strong or unique.

Describe the collaborative process and methods of communication, including areas of potential collaboration and areas of focused collaboration. If collaborating entities are physically separated it is especially critical to describe in detail the anticipated frequency of specific modes of communication/interaction.

Show that the research projects proposed for the CERC do not overlap in purpose or intent with existing NIH-funded grants, but will constitute new activities or a natural progression of current research.

Following item j: Include letters (on institutional letter head) from each proposed project Leader and Core Leader confirming his/her role in the proposed Center, as well as from institutional officials confirming their commitment to the project.

Specific instructions for individual projects

A cover page is required for each research project and should include the number and title of the project. Use numbers (1,2,3, etc.) to designate individual research projects. Give each project a title and provide the names and titles of the project leader and of participating investigators.

Form page 2

For each proposed project, provide a Description (abstract) of the proposed research according to the instructions for form page 2. In addition, the Description should contain a brief description of how the research project will contribute to attainment of the CERC program objectives.

Under "key personnel", follow the standard instructions, listing all key personnel participating in the project, beginning with the project leader. Distinguish co-investigators from other key personnel.

Form page 3

Prepare a table of contents for each research project using form page 3. Since the biographical sketches of all participating investigators will be located at the end of the overall application and therefore should be referenced in the overall table of contents, it is not necessary to repeat these pages.

Research plan (a-d)

Do not exceed a total of 25 pages for Items a-d in the Research Plan for each individual project. Tables, charts, graphs, diagrams and figures must be included within the 25-page limit. Applications that exceed the 25-page limit or NIH requirements for type size and margins (refer to instructions for details) will be returned to the applicant without further consideration. The 25-page limit does not include Items e-i (Human Subjects, Vertebrate Animals, Literature Cited, Consortia and Consultants/Collaborators).

Item A - Specific aims (typically one page): List in priority order the broad, long-range objectives of the proposed project and describe concisely and realistically the more immediate goals. In addition, state the project's relationship to the CERC program goals and how it relates to other research projects within the CERC and to the cores.

Item B - Background and significance: Use this section to describe how the proposed research will contribute to meeting the goals and objectives and explain the rationale for the selection of the general methods and approaches proposed to accomplish the specific aims. In addition to the overall biological significance of the proposed research, this section should indicate the relevance of the project to the theme of the CERC.

A progress report must be provided for each project proposed for continuation in competing continuation applications. Provide the beginning and ending dates for the period covered since the project was last reviewed competitively. Summarize the specific aims of the project from the previous application and the importance of the findings. Discuss any changes in the specific aims as a result of budget reductions. Include the complete references to appropriate publications and manuscripts accepted for publication (the reference list is not included towards the 25-page limit for Items a-d).

Item D - Research design and methods: The conceptualization and planning of the project must be sufficient to allow for an assessment of the project's potential. The proposed research must be presented in sufficient detail to allow evaluation of the proposed methods. Appropriate expertise to conduct the proposed research must be included among the key personnel, e.g., for research involving human subjects, statistical and/or clinical trial design expertise (as appropriate) is essential during the design and conduct of research. .

Appendix. No appendix need be provided for individual projects, as a single appendix is to be provided for the entire CERC application.

Checklist. Not required for individual projects. Submit a single checklist for the entire application.

Specific instructions for cores

A cover page is required for each core and should include the title and letter designation of the core and provide the names and titles of the core leader and of participating investigators.

The CERC application must include an administrative core. Additional scientific cores may be included if they contribute to two or more projects.

Administrative core. The applicant (awardee) institution and the Principal Investigator will be responsible for the application and for collaborative research activities in the CERC program. The awardee institution will be legally and financially responsible and be accountable for the use and disposition of funds awarded to the application, and will attest to the availability of personnel and facilities capable of performing and supporting the administrative functions of the CERC program.

Funding for the overall administrative efforts including secretarial, and other administrative services, travel to the annual NCCAM Centers meeting, expenses for publications produced by the project, communication expenses including organization of External Advisory Council meetings, etc., should be requested here.

Scientific core(s). A scientific core is a resource to the CERC grant as a whole. The application must indicate the specific projects it will serve. Each core must be utilized by two or more of the projects proposed for the CERC. This section should present a clear picture of the facilities, techniques, and skills that the core will provide. The role of the core leader and each of the key participants should be described. The apportionment of dollars, or percentage of dollars, that will be required to support each component research project which will utilize each scientific core should be presented.

Form page 2

Provide a description (abstract) of the core activities and services according to the instructions on form page 2. In addition, the abstract should contain a brief description of how the core services will contribute towards attainment of the CERC program objectives.

Form page 3

Prepare a table of contents for each core using form page 3. Since the biographical sketches of all participating investigators will be located at the end of the overall application (and therefore should be referenced in the overall Table of Contents), it is not necessary to repeat these pages.

Core plan

The research (core) plan (items a-d) for each core section is limited to 25 pages.

Item A - Specific aims: State the core's relationship to the CERC goals and how it relates to the research projects in the application.

Item B - Background and significance: Use this section to describe how the proposed core activities will contribute to meeting the goals and objectives and explain the rationale for the selection of the general methods and approaches proposed to accomplish the specific aims. These resources should not duplicate resources already available to study investigators. In addition, this section should indicate the relevance of the core activities to the primary theme of the CERC.

Item C – Preliminary studies/progress: A progress report must be provided for each core proposed for continuation in competing continuation applications. Provide the beginning and ending dates for the period covered since the core was last reviewed competitively. Summarize the specific aims of the core from the previous application and the importance of the findings. Discuss any changes in the specific aims as a result of budget reductions. Include the complete references to appropriate publications and manuscripts accepted for publication (the reference list is not included towards the 25-page limit for Items a-d).

Appendix.

Provide ONE appendix for the entire application, following all projects and cores. Otherwise follow the standard instructions, providing five copies of the single appendix for the entire document. Up to ten publications per project/core may be included in the appendix. Order of materials in the appendix should follow that of the application, i.e., starting with materials relevant to the overall program, continuing with materials relevant to the individual projects, and concluding with any materials relevant to the core(s). Every appendix item pertaining to a specific project or core must be clearly labeled as such.

Please do not staple the appendix. Sections may be separated, for example, by interpolating sheets of colored paper.

Prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed research

Name, address, and telephone number of the Principal Investigator

Names of other key personnel

Participating institutions

Number and title of this funding opportunity

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning of this document.

Applications must be prepared using the research grant application forms found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

3.C. Application ProcessingApplications must be received on or before the application receipt/submission date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review.

Upon receipt applications will be evaluated for completeness by CSR. Incomplete applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such applications must include an Introduction addressing the previous critique.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements

Each CERC application must demonstrate that the following Special Requirements and provisions are met. Further requirements are explained under the heading "Supplemental Instructions" in Section IV.2, above.

Applicants must:

Attach letters of support from an appropriate, high-ranking official at the applicant institution and from each collaborating institution(s), documenting significant institutional commitment to the Center and to the collaboration;

Delineate how different components of the CERC, including key personnel, will interact, why they are essential to accomplishing the overall goal of the research, and how the combined resources create capabilities that are more than the sum of the parts, i.e., how the various components of the CERC will inform and contribute to each others’ scientific growth;

Describe the collaborative process and methods of communication, and identify areas of potential collaboration and areas of focused collaboration. Address specifically how the effects of separation will be managed, if any component of a proposed Center is physically separated from the others (i.e., in a different department or institution), describing the frequency of use of different methods of interaction

Describe scientific and/or programmatic synergy between projects, and between projects and proposed cores (i.e., the interactions between projects and with the cores must result in a program where the whole is greater than the sum of its parts). Shared use of analytical facilities or projects does not, in itself, constitute synergy, which is provided by the potential of the projects and/or cores to scientifically enhance each other. Each core must contribute to at least two of the proposed projects.

Show that research projects proposed for the CERC do not overlap in purpose or intent with existing NIH-funded grants, but will constitute new activities or a natural progression of current research.

Plan to participate, with collaborators, in an annual two-day meeting in the Baltimore-Washington area with other NCCAM-funded center P.I.s. Travel costs for this purpose should be included in the proposed budget for the application, in the Administrative Core.

Describe plans for an External Advisory Committee (EAC). Specific expertise required of EAC members should be specified but the names of individuals should not be provided.

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

Applicants requesting more than $500,000 in direct costs in any year of the proposed research must include a plan for sharing research data in their application. The funding organization will be responsible for monitoring the data sharing policy (http://grants.nih.gov/grants/policy/data_sharing).

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information

1. CriteriaOnly the review criteria described below will be considered in the review process.

Applications that are complete will be evaluated for scientific and technical merit by an appropriate review group convened by NCCAM in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score.

Receive a written critique

Receive a second level of review by the National Advisory Council for Complementary and Alternative Medicine.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the Project Leader(s) and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

Progress: A progress report must be provided for each project proposed for continuation in competing continuation applications. Provide the beginning and ending dates for the period covered since the project was last reviewed competitively. Summarize the specific aims of the project from the previous application and the importance of the findings. Discuss any changes in the specific aims as a result of budget reductions. Include the complete references to appropriate publications and manuscripts accepted for publication (reference list is not included in the 25-page limit).

Based on the evaluation described above, each project will receive a numerical score from 1.0 to 5.0.

B) Cores

Each core will receive a merit descriptor (outstanding, acceptable, unacceptable) that reflects:

Technical merit and justification of the proposed core;

Qualifications, experience, and commitment of the personnel involved in the core;

Adequacy of plans for use of the core by the research projects and the benefit to the projects from core resources; and

Adequacy of day-to-day administration, as well as program coordination and ongoing evaluation of the center (administrative core)

A progress report must be provided for each core proposed for continuation in competing continuation applications. Provide the beginning and ending dates for the period covered since the project was last reviewed competitively. Summarize the specific aims of the core from the previous application and the importance of the findings. Discuss any changes in the specific aims as a result of budget reductions. Include the complete references to appropriate publications and manuscripts accepted for publication (not part of the page limitations).

C) Principal Investigator

The P.I will be evaluated with respect to:

Leadership and scientific ability to develop a program of integrated research projects with a well-defined central research focus; and

Time commitment of a minimum of 25% effort.

D) Resources and Environment

Institutional commitment to the program;

The extent to which CAM investigators and clinicians are involved in the research, if appropriate;

The intellectual and physical resources available to the program project participants; and

Adequacy of facilities to support the proposed research, including clinical facilities, laboratory facilities and data management systems, when needed.

E) Program Synergy

Each application will receive a merit descriptor (highly integrated, integrated, not integrated) that reflects the degree of synergy of the proposed CERC. In particular, program synergy will be evaluated on:

The potential for scientific impact of the proposed CERC, which should be greater than that the sum of its component research projects and cores, i.e., the proposed components should interact synergistically, in that the projects/cores should have the potential to scientifically enhance each other.

Demonstration of an effective relationship among collaborating departments and institutions where appropriate, including documentation of current relationships, as well as the functions, commitments and contributions that each collaborating member will bring to the proposed project.

The nature, scope, and effectiveness of the plans for communication, coordination, and collaboration among research project investigators.

F) Additional Criteria for Competing Renewal Applications

Each application will receive a merit descriptor (outstanding, acceptable, unacceptable) that reflects the progress of the investigators since the initial award, evaluated on:

The progress and achievements specific to this program project since the initial competitive review

Evidence that scientific synergy has occurred as indicated by joint publications and new collaborative aims and/or projects

Evidence that the previous Specific Aims have been accomplished and that the new research goals are logical extensions

The previous performance and cost-effectiveness of the cores

The justification for adding new projects or cores or deleting components previously supported.

G) Overall Program

A single numerical priority score will be assigned to the CERC application as a whole.

In assigning the priority score for the application as a whole, although primary emphasis will be placed on scientific merit of the research projects, and past productivity (where applicable), significant consideration will also be given to the strength of core(s), leadership ability of the P.I., institutional commitment, resources and environment, and program synergy.

An application in which the reviewers consider no more than two component research projects to be of substantial and significant scientific merit will not satisfy the requirements for this P01 award, and therefore will be recommended for "no further consideration."

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates
Not applicable

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 14 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

Human Subjects Protection:Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

Required Education on the Protection of Human Subject Participants:NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy:NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

Standards for Privacy of Individually Identifiable Health Information:The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002 . The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.